Phosphodiesterase type 5 (PDE5) is co-localized with key proteins of the nitric oxide/cyclic GMP signaling in the human prostate

Purpose

Experimental studies have provided the basis for the evaluation of inhibitors of the phosphodiesterase type 5 (PDE5) in the treatment of lower urinary tract symptomatology (LUTS) secondary to benign prostatic hyperplasia (BPH). It has been speculated that the clinical efficacy of PDE5 inhibitors in patients with LUTS/BPH can be explained by their effects on the urinary bladder rather than on the prostate. Hence, the significance of the nitric oxide (NO)/cyclic GMP signaling in the control of the human prostate requires further clarification.

Methods

The present study aimed to investigate by means of immunohistochemistry in the human prostate the expression and distribution of key mediators of the NO pathway, namely cyclic GMP, the neuronal nitric oxide synthase (nNOS), and cyclic GMP-binding protein kinases type I (cGKIα, cGKIß), in relation to PDE5, protein kinase A (cAK), and the vasoactive intestinal polypeptide (VIP).

Results

In the smooth muscle portion of the transition zone, immunosignals specific for the PDE5 were found co-localized with cyclic GMP, cGKIα, and cGKIß, as well as with the cyclic cAMP-binding protein kinase A. Smooth muscle bundles were seen innervated by slender varicose nerves characterized by the expression of nNOS. Some of these nerves also presented staining related to the neuropeptide VIP.

Conclusions

The findings give hints that the cyclic GMP- and cyclic AMP-dependent signal transduction may synergistically work together in regulating muscle tension in the transition zone. This might be of significance for the identification of new pharmacological avenues to treat patients with symptomatic BPH.     

Stromal and acinar components of the transition zone in normal and hyperplastic human prostate

OBJECTIVE: To analyse the histological components of the transition zone in both normal human prostate and benign prostatic hyperplasia (BPH), and to determine the volumetric density (Vv) of the different elements (connective tissue, smooth muscle cells, acini and total stroma). MATERIALS AND METHODS: Samples of BPH tissue from the transition zone were obtained from 16 patients with clinical symptoms of bladder outlet obstruction who underwent open prostatectomy. The control samples comprised 16 transition zone samples from prostates obtained during necropsy of adults aged < 30 years (killed in accidents). The Vv of these components was determined by stereological methods. RESULTS: The mean (sd) Vv in the controls and BPH samples were, respectively: connective tissue 40.47 (5.16) and 46.71 (9.91)%; smooth muscle cells 24.86 (2.74) and 31.56 (5.49)%; acini 28.73 (6.25) and 17.78 (10.87)%; all differences were statistically significant. CONCLUSIONS: These results confirm the hypothesis that in BPH there is an increase in the stromal component, both smooth muscle fibres and connective tissue.     

Immunohistochemical distribution of cAMP- and cGMP-phosphodiesterase (PDE) isoenzymes in the human prostate

OBJECTIVES: With the introduction of sildenafil citrate (Viagra), the concept of phosphodiesterase (PDE) inhibition has gained tremendous interest in the field of urology. Cyclic nucleotide second messengers cGMP and cAMP have been assumed to be involved in the control of the normal function of the prostate. The aim of the present study was to evaluate by means of immunohistochemistry the expression and distribution of some cAMP- and cGMP-PDE isoenzymes in the prostate. MATERIAL & METHODS: Cryostat sections (10 microM) of formaldehyde-fixated tissue segments excised from the transition zone of human prostates were incubated with primary antibodies directed against the PDE isoenzymes 3, 4, 5, and 11. Then, sections were exposed to either fluorescein isothiocyanate- (FITC) or Texas Red- (TR) labeled secondary antibodies and visualization was commenced by means of laser fluorescence microscopy. RESULTS: TR-immunofluorescence indicating the presence of PDE4 (cAMP-PDE) was abundantly observed in the fibromuscular stroma as well as in glandular structures of the transition zone. In contrast to the distribution of PDE4, immunoactivity indicating PDE5 (cGMP-PDE) and 11 (dual substrate PDE) was mainly observed in glandular and subglandular areas. No immunostaining for PDE3 (cGMP-inhibited PDE) was detected. CONCLUSION: Our results confirm the presence of PDE isoenzymes 4, 5 and 11 in the transition zone of the human prostate and present evidence that these isoenzymes are not evenly distributed. These findings are in support of the hypothesis that there might be a rationale for the use of PDE inhibitors in the pharmacotherapy of BPH and LUTS.     

The nitric oxide pathway in the human prostate: clinical implications in men with lower urinary tract symptoms

To date, there is an increasing interest in the nitric oxide (NO) pathway as a potential pharmacological target to treat male lower urinary tract symptomatology (LUTS). In the transition zone of the human prostate, a dense nitrinergic innervation has been shown of the fibromuscular stroma, glandular epithelium and blood vessels. The expression of key proteins of the NO pathway, such as the endothelial and neuronal nitric oxide synthase (eNOS, nNOS), cGMP-degrading phosphodiesterase type 5 (PDE5) and cGMP-binding protein kinase (cGK), has also been demonstrated. The hypothesis that an impaired NO/cGMP-signaling may contribute to the pathophysiology of benign prostatic hyperplasia (BPH) is supported by the results from randomized, placebo-controlled clinical studies, indicating that NO donor drugs and PDE5-inhibitors sildenafil, tadalafil and vardenafil may be useful to treat storage and voiding dysfunctions resulting from LUTS in men. Thus, given a potential role of the NO-pathway in the prostate and/or in other parts of lower urinary tract (e.g. bladder), the enhancement of the NO signaling by NO donor drugs, PDE5 inhibitors or activators of the soluble guanylyl cyclase (sGC) may represent a new therapeutic strategy for the treatment of LUTS. This review serves to focus on the role of NO and the NO-dependent signaling in the control of smooth muscle function in the human prostate. Results from clinical trials in men with LUTS/BPH are also discussed.     

Nitric oxide/cGMP-mediated effects in the outflow region of the lower urinary tract—is there a basis for pharmacological targeting of cGMP?

Treatment with α-adrenoceptor antagonists that reduce the tone of prostatic stromal and urethral smooth muscle has beneficial effects in patients with benign prostatic hyperplasia (BPH) and lower urinary tracts symptoms (LUTS) and has brought attention to regulatory mechanisms of smooth muscle contractility of the outflow region. The prostate, urethra and bladder neck are densely supplied by nitric oxide (NO)-synthase—containing nerves that cause relaxation upon activation. In various experimental models, altered function or activity of the NO/cGMP pathway of the bladder neck and urethra may be related to inappropriate or un-coordinated functions of the bladder outlet and detrusor, but causal connections between alterations in this signaling system, a dysfunctional bladder outlet, and the development of LUTS are not established for humans. The present review focuses on regulatory functions of smooth muscle contractility by the NO/cGMP-pathway in the bladder neck, urethra, and prostate. Disease-related alterations in the NO/cGMP-pathway, and putative options for pharmacological modification of this signaling pathway in the out-flow region are briefly discussed.     

The Mechanism of Action of Phosphodiesterase Type 5 Inhibitors in the Treatment of Lower Urinary Tract Symptoms Related to Benign Prostatic Hyperplasia

Context

Clinical trials of phosphodiesterase type 5 inhibitors (PDE5-Is) have consistently demonstrated a significant reduction in lower urinary tract symptoms (LUTS) and small urinary flow rate changes in men with benign prostatic hyperplasia (BPH).

Objective

This review presents the proposed mechanisms of action of PDE5-Is in the treatment of BPH-LUTS focusing on the localization of PDE5 isoenzymes in the pelvic structures; smooth muscle relaxation in the bladder, prostate, and supporting vasculature; increased blood perfusion of the bladder and prostate; and modulation of sensory impulses from these organs.

Evidence acquisition

Literature describing in vitro, preclinical, or clinical studies of pathologic processes contributing to LUTS or effects of PDE5 inhibition on the lower urinary tract (LUT) was selected for review.

Evidence synthesis

We objectively assessed and summarized the published data focusing on articles published within the past 10 yr. Articles before the time cut-off were included if historically relevant.

Conclusions

The PDE5 isoenzymes are highly expressed in the LUT including the bladder, prostate, and their supporting vasculature. In vitro assays have demonstrated PDE5-Is by regulating cyclic guanosine monophosphate (cGMP) degradation and enhancing the nitric oxide/cGMP signaling pathway to relax human smooth muscle strips from the prostate, bladder, and LUT arteries. In animals characterized by ischemia/hypoxia of the genitourinary tract, treatment with PDE5-Is increases bladder and prostate tissue oxygenation. PDE5-Is have been shown to reduce nonvoiding contractions and bladder afferent nerve firing in decerebrate spinal cord–injured rats, and to reduce mechanosensitive afferent activities of both Aδ- and C-fibers in an irritated or overextended bladder model.     

cGMP-enhancing- and alpha1A/alpha1D-adrenoceptor blockade-derived inhibition of Rho-kinase by KMUP-1 provides optimal prostate relaxation and epithelial cell anti-proliferation efficacy

BACKGROUND: Soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) and Rho kinase (ROCK2) pathways are important in the regulation of prostate smooth muscle tone. This study is aimed to examine the relaxation activities of a sGC activator and PDE5A/ROCK2 inhibitor KMUP-1 in rat prostate and associated anti-proliferation activity in human prostatic epithelial cells. METHODS: The action characteristics of KMUP-1 were identified by isometric tension measurement, receptor binding assay, Western blotting and radioimmunoassay in rat prostate. Anti-proliferation activity of KMUP-1 in human prostatic epithelial PZ-HPV-7 cells was identified using flow cytometry and real time QRT-PCR. RESULTS: KMUP-1 inhibited phenylephrine-induced contractility in a concentration-dependent manner. KMUP-1 possessed potent alpha(1A/)alpha(1D)-adrenoceptor binding inhibition activity, increased cAMP/cGMP levels and increased the expression of sGC, PKG, and PKA protein in rat prostate. Moreover, KMUP-1 inhibited phenylephrine-induced ROCK2 expression. KMUP-1 inhibited cell growth, arrested the cell cycle at G(0)/G(1) phase and increased the expression of p21 in PZ-HPV-7 cells. CONCLUSIONS: These results broaden our knowledge of sGC/cGMP/PKG and ROCK2 regulation on the relaxation and proliferation of prostate, which may help in the design of benign prostate hyperplasia (BPH) therapies that target these signaling pathways. KMUP-1 possesses the potential benefit in the treatment of BPH by its alpha(1A/)alpha(1D)-adrenoceptor blockade, sGC activation, inhibition of PDE5A and ROCK2 and p21 protein enhancement, leading to attenuation of the smooth muscle tone and the proliferation of epithelial PZ-HPV-7 cells. The synergistic contribution of these pathways by KMUP-1 may benefit BPH patients with lower urinary tract symptoms.     

前列腺纤维化的研究进展

部分表现为下尿路症状(LUTS)的患者前列腺体积并不大,有证据支持前列腺纤维化是除BPH、平滑肌功能障碍之外,导致LUTS的原因之一。研究表明,前列腺纤维化的发生与各种原因导致的炎症、缺血缺氧、药物相关,具体机制涉及肌成纤维细胞的分化、聚集和活化。因此,抗炎、抗纤维化可能是治疗LUTS的潜在作用靶点。本文就前列腺纤维化的成因、诊断、与LUTS的关系及治疗进展作一综述。     

Alpha 1-adrenoceptor antagonists terazosin and doxazosin induce prostate apoptosis without affecting cell proliferation in patients with benign prostatic hyperplasia.

PURPOSE: Recent evidence indicated that an alpha 1 blocker, doxazosin, induces prostate apoptosis in patients with benign prostatic hyperplasia (BPH). In this study, to determine whether this apoptotic response was mediated by alpha 1 adrenoceptor-dependent mechanism or was specific to doxazosin, we examined the effect of another alpha 1 blocker, terazosin, in addition to doxazosin, on the dynamics of prostate cell growth. MATERIALS AND METHODS: Cell proliferation and apoptosis were evaluated in BPH patients, an untreated (control) group (n = 31), and men treated with terazosin (n = 42) and doxazosin (n = 61) for the relief of the obstructive symptoms. Terazosin (1 to 10 mg./day) and doxazosin (2 to 8 mg./day) treatment varied from 1 week to 3 years. Ki-67 immunostaining and the TUNEL assay were used to evaluate the proliferative and apoptotic indices, respectively, in both the epithelial and stromal components of prostate (biopsy and prostatectomy) specimens. The smooth muscle cell content of the prostatic stroma was identified on the basis of smooth muscle alpha-actin immunoreactivity. RESULTS: A significant induction of apoptosis was observed in both the prostatic epithelial and stromal cells within the first month of terazosin and doxazosin therapy, as compared with untreated controls (p < 0.05). Furthermore, the marked induction of prostatic stroma apoptosis in response to both alpha 1 adrenoceptor antagonists was paralleled by a significant decrease in the smooth muscle alpha-actin expression. This loss of prostatic smooth muscle cells correlated with morphological stromal regression (as detected by trichrome staining) and BPH symptom improvement. Neither terazosin nor doxazosin therapy resulted in significant changes in prostate cell proliferation. CONCLUSIONS: These findings demonstrate that alpha-blockers as a class may regulate prostate growth by inducing apoptosis in both the epithelial and stromal cells, with little effect on cell proliferation. Apoptosis-mediated prostate stromal regression appears as a molecular mechanism underlying the therapeutic response to alpha 1 blockade in the treatment of BPH.     

Activity of phosphodiesterase type 5 inhibitors in patients with lower urinary tract symptoms due to benign prostatic hyperplasia

Study Type – Therapy (RCT) Level of Evidence 1b What’s known on the subject? and What does the study add? Phosphodiesterase type 5 inhibitors (PDE 5Is) improve erectile function and lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH), however the exact effects on prostate tissue and its underlying mechanisms remain unclear. PDE 5Is enhanced the production of cyclic nucleotides in the plasma and prostate, and the distribution of PDE 5Is in the prostate was higher than in the plasma.

OBJECTIVE

? To evaluate the impact and distribution of a single phosphodiesterase type 5 inhibitor (PDE5 I) dose (udenafil or tadalafil) in prostate tissue and plasma in patients with benign prostatic hyperplasia (BPH).

PATIENTS AND METHODS

? Thirty BPH patients complaining of erectile dysfunction along with moderate‐to‐severe lower urinary tract symptoms (LUTS) who underwent transurethral resection of the prostate (TURP) were enrolled in the present study. ? The patients were randomly divided into the three groups: group 1, TURP without PDE5 Is; group 2, 200 mg of udenafil given 1 h before TURP; and group 3, 20 mg of tadalafil given 1 h before TURP. ? We evaluated the concentrations of PDE5‐I, cAMP and cGMP in prostate tissues and plasma, and calculated the prostate tissue‐to‐plasma (T/P) ratio.

RESULTS

? The concentration of udenafil in prostate tissue and plasma was 2028.6 ± 360.8 ng/g and 463.7 ± 39.1 ng/mL, respectively, and the resulting T/P ratio was 4.4. The tadalafil concentration in prostate tissue and plasma was 385.7 ± 83.8 ng/g and 305.8 ± 41.1 ng/mL, respectively, and the T/P ratio was 1.3. ? Udenafil and tadalafil significantly increased the cAMP and cGMP levels in plasma and prostate tissues.

CONCLUSIONS

? Udenafil and tadalafil significantly increased cAMP and cGMP levels and were more highly distributed in the prostate than plasma. The T/P ratio of udenafil was higher than tadalafil. ? These findings may help in the assessment of the feasibility of using PDE5 Is to concurrently treat both LUTS and erectile dysfunction.     

Presence and passage dependent loss of biochemical M3 muscarinic receptor function in human detrusor cultured smooth muscle cells

PURPOSE: We explored morphological and biochemical aspects of human detrusor cells in culture as a tool for investigating the physiological mechanisms underlying bladder function and disturbances. MATERIALS AND METHODS: Primary cultures of smooth muscle cells were derived from human bladder specimens of patients with an average age of 70 years undergoing cystectomy. Cultured cells were investigated by morphological, immunocytochemical and Western blot analysis. The alpha-actin content as well as the presence of muscarinic M2 and M3 receptors was determined in cell lysates and in fresh tissue homogenate for comparison. The functional response to muscarinic stimulation was assessed by measuring IP3 production induced by 1 mM. carbachol. RESULTS: Cultured smooth muscle cells showed a characteristic spindle-shaped morphology at early passages. Similarly immunocytochemical and Western blot analysis revealed an alpha-actin cell content that was unmodified up to passage 3. Conversely this marker protein sharply decreased during further passages. M3 muscarinic receptor was present in cultured cells and fresh tissue homogenates, whereas the M2 subtype was evident only in homogenates. Carbachol produced a time dependent increase in IP3 cell content, reaching maximal production after 20 minutes of exposure. This response was passage sensitive. CONCLUSIONS: Cultured human detrusor smooth muscle cells maintain their morphological and biochemical characteristics up to passage 3. With this caveat such cells can be an appropriate tool for investigating the molecular pathways underlying cholinergic activation in normal physiological and pathological bladders, and accordingly for detecting putative targets for pharmacological intervention.     

Alpha-adrenoceptors are a common denominator in the pathophysiology of erectile function and BPH/LUTS--implications for clinical practice

A literature search of PubMed documented publications and abstracts from proceedings of scientific meetings was made to review the available data on benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) and erectile dysfunction (ED) with a special focus on the role of alpha-adrenoceptors as critical mediators of pathophysiology. The reader is introduced to clinical results on the therapeutic potential of alpha-blockers alone and in combination with phosphodiesterase type 5 (PDE-5) inhibitors in the treatment of ED associated with LUTS/BPH. Epidemiological studies clearly show that an association exists between ED and LUTS/BPH. The severity of LUTS is correlated with the risk for ED. A significant number of LUTS/BPH patients are nonresponsive to the common ED treatment with PDE-5 inhibitors. As smooth muscle contractility is regulated by adrenoceptors in the corpus cavernosum, prostate and detrusor, the alpha-adrenoceptor system may be considered a common pathophysiological mediator in the development of ED and LUTS/BPH. Blockade of alpha-adrenoceptors for the treatment of BPH/LUTS may have the potential of improving sexual function. Conversely, PDE-5 inhibitors may exhibit positive effects in LUTS patients. Pilot studies on combination regimens of alpha-adrenoceptor antagonists and PDE-5 inhibitors have yielded encouraging results in LUTS patients with persistent ED. On the basis of pharmacological and clinical evidence, it is established that the alpha-adrenoceptor system plays an important role in the pathophysiology of ED and LUTS secondary to BPH. Larger trials on the combination of alpha-adrenoceptor antagonists with PDE-5 inhibitors are necessary to develop an integrated treatment approach for BPH/LUTS patients with comorbid ED.     

INDUCTION OF PROSTATE APOPTOSIS BY DOXAZOSIN IN BENIGN PROSTATIC HYPERPLASIA

Purpose

The molecular mechanisms underlying the therapeutic effect of the alpha 1 blocker, doxazosin, on benign prostatic hyperplasia (BPH) are poorly understood. We evaluated the effect of doxazosin on cell proliferation and apoptosis in the prostatic glandular epithelium and stroma of patients with BPH.

Materials and Methods

We examined proliferative and apoptotic activities in prostate specimens of 22 men a mean of 65 years old with BPH before and after doxazosin treatment within the normal therapeutic range. Proliferative and apoptotic indexes were determined using Ki-67 nuclear antigen staining and the terminal transferase end labeling assay, respectively. The smooth muscle cell content in prostatic specimens was identified by smooth muscle alpha-actin, and desmin immunoreactivity and apoptotic indexes were correlated with prostatic stromal tissue regression and improvement in BPH symptoms.

Results

In response to doxazosin treatment there were no significant changes in the kinetics of cell proliferation in the prostatic epithelial or stromal cell population. Mean pretreatment baseline apoptosis was 1.9 and 1.0% for the epithelial and stromal prostate components, respectively. Mean apoptotic indexes significantly increased after 3 months of doxazosin treatment in the glandular epithelial (6%) and smooth muscle cells (15%). By 12 months after treatment epithelial apoptosis had decreased to constitutive levels, while the apoptotic index of prostatic stroma cells remained high. Doxazosin induced smooth muscle cell apoptosis correlated with prostatic stromal degeneration, decreased alpha-smooth muscle actin expression and improved BPH symptoms.

Conclusions

These findings implicate the induction of prostate apoptosis by doxazosin as a potential molecular mechanism underlying the acute and chronic therapeutic responses of BPH to alpha 1 blockade.     

α1-Adrenoceptor subtypes and lower urinary tract symptoms

Abstract:   Benign prostatic hyperplasia (BPH) is a common cause of urinary outflow obstruction in aging men leading to lower urinary tract symptoms (LUTS). α₁-Adrenoceptors (α₁ARs) antagonists (blockers) have become a mainstay of LUTS treatment because they relax prostate smooth muscle and decrease urethral resistance, as well as relieving bladder LUTS symptoms. A review of key recent clinical trials suggests new insights into the role of specific α₁AR subtypes in the treatment of LUTS.     

Lower urinary tract symptoms and sexual dysfunction: epidemiology and pathophysiology

There is ample evidence from many epidemiological studies that lower urinary tract symptoms (LUTS) and sexual dysfunction are strongly linked, independently of age and comorbidities such as hypertension, diabetes, dyslipidaemia and coronary heart disease. However, a causal link between both conditions is not yet established. Four pathophysiological mechanisms currently support the relationship between LUTS and erectile dysfunction (ED): (i) The nitric oxide synthase (NOS)/NO theory; there is a reduction in NOS-containing nerves in the prostate and bladder/urethra in patients with bladder outlet obstruction (BOO), and that lack of NO or loss of protein kinase G causes ED; (ii) The autonomic hyperactivity and metabolic syndrome hypothesis: benign prostatic hyperplasia (BPH) may be part of the metabolic syndrome, which includes cardiovascular diseases (e.g. hypertension, ischaemic heart disease) and diabetes mellitus, known risk factors for ED. Hypertension, obesity, and hyperinsulinaemia have all been claimed to be associated with an increased sympathetic activity. Increased sympathetic activity is involved in LUTS/BPH and may have a role in ED/sexual dysfunction, with noradrenaline and alpha1-adrenoceptors representing a common link; (iii) the Rho-kinase activation/endothelin pathway; there can be increased Rho-kinase activity, and consequently calcium sensitivity of the contractile machinery, in prostate smooth muscle in BPH, the detrusor in BOO, corpora cavernosa in ED, and in the resistance vessels in hypertension. The actions of several factors beside noradrenaline (e.g. endothelin-1, angiotensin II), possibly involved in the increased smooth muscle activity found in both LUTS/BPH and sexual dysfunction, are dependent on Rho-kinase activity. Thus increased Rho-kinase activity might represent a common link between LUTS and sexual dysfunction; (iv) Pelvic atherosclerosis; animal models mimicking pelvic ischaemia and hypercholesterolaemia show similar smooth muscle alterations of the detrusor and corpora. Pelvic ischaemia may induce the biological modifications described above and may thus represent as well a common link between LUTS and sexual dysfunction. Studies treating one condition (e.g. ED) and measuring the impact on the other (e.g. LUTS) should further contribute to support this common link.     

Embryologic development of the prostate. Insights into the etiology and treatment of benign prostatic hyperplasia.

Pharmacologic strategies for the treatment of BPH are at present directed toward relaxing prostate smooth muscle and reducing prostate volume. Historically, the primary limitation of pharmacotherapy for BPH has been that the symptomatic improvement achieved was overshadowed by the morbidity of treatment. However, the morbidity has been markedly diminished based on a more precise understanding of the embryology, physiology, and pharmacology of the prostate. The origins and pharmacologic properties of the smooth musculature of the prostate and bladder are unique. Therefore, drugs such as alpha blockers may relax the prostate selectively without altering bladder function. Although phenoxybenzamine, a nonselective alpha blocker, relieves infravesical obstruction secondary to BPH, the severity of the adverse reactions limits the use of this drug. The contractile properties of the prostate smooth muscle are mediated by alpha-1 adrenoceptors. The effectiveness of phenoxybenzamine and selective alpha-1 blockers such as prazosin and terazosin are similar. The side effects of the selective alpha-1 blockers are negligible. Androgen suppression, which lowers testosterone, produces intolerable side effects such as gynecomastia, erectile dysfunction, and impaired libido. The androgen dependency of the prostate provides the rationale for using 5 alpha-reductase inhibitors for the treatment of BPH. Reduction of prostate volume can be achieved by blocking the action or synthesis of dihydrotestosterone without impotence, gynecomastia, and hot flashes. These recent advances in pharmacotherapy for BPH are based on understanding of the fundamental developmental properties of the prostate.     

良性前列腺增生症组织形态学及临床相关因素分析

目的 :探讨良性前列腺增生症 (BPH)临床参数与其组织学改变的关系 ,以指导临床治疗方法的选择。方法 :应用 HE染色和 Masson染色结合计算机辅助图像分析的方法 ,对 30例 BPH前列腺组织构成成分和 5例正常前列腺组织进行了形态学的定量分析。结果 :1BPH前列腺组织中上皮、腺腔、结缔组织和平滑肌的面积百分比分别是 14.87%± 5 .90 %、 2 2 .5 4%± 6 .99%、2 4.6 0 %± 7.78%和 37.98%± 9.33%。间质∶上皮为 (5 .30±3.78)∶ 1,平滑肌∶间质为 (0 .6 1± 0 .12 )∶ 1。 2随着腺体重量的增加 ,上皮面积百分比增加 (P <0 .0 1) ,平滑肌面积百分比下降 (P <0 .0 5 )。 3 BPH前列腺组织标本中的平滑肌面积百分比与 IPSS呈明显正相关 (P <0 .0 1)。结论 :1BPH的前列腺以间质增生为主 ,且间质中的平滑肌增生更为突出。2 BPH患者的 IPSS与 BPH的组织成分之间存在一定的关系 ,对临床患者的治疗选择有指导意义。